Structures of the Protein
'Structures of the Protein. ' 'What does Primary, secondary, therchary, quartiary, structure mean?' A protein has 3 structures and when combined with another protein, even 4 types of structures. The Primary structure is the Amino Acid sequence. AA sequence is important for several reasons, sequence determination is part of molecular pathology, an emerging area of modern medicine. The Secondary structure is the common shapes that occur, alpha helix, beta sheet and the other minor structures that are repeatitive enough to carry a shape. The tertiary is an ensemble of the backbone polypeptide's 3D structure including the disulphide bridge. Quartiary would be multiple polypeptide units interacting. Protein structures in the most basic terms are: Primary Structure (PS) - ' is determined by the sequence of amino acids & disulphide locations making up the backbone, not the shape or position of the backbone. '''Secondary Structure (SS) - ' is the backbone's Spacial arrangements, Alpha Helix, and Beta Sheets that define the shape of the backbone. These are held in shape by hydrogen bonds. This does not include loops because the shapes of the loops are not defined. '''Super Secondary Strucure (SSS) - is a cluster or pattern in SS (bAb unit) Tertiary Structure (TS) - is the position of the protein's amino acid sidechains and the hydrogen bonds that holds the protein together into a completed unit. The structure of the whole protein forms the isosurface. - Spacial interaction as whole. Change any of the first 3 structures and you will change the isosurface. Quartiery Structure (QS) - ' is the outside shape of a native protein's isosurface, and how closely it fits into another protein's isosurface. This is how many different whole protein sub-units fit together, like puzzle peices, into larger micro structures. We see this on foldit in Docking, Interface, and Symmetric puzzles, where smaller sub-unit proteins snuggle up close together forming larger structures. Fits like a key in a lock. Multiple polypeptide chain, subunit interaction. 'Recipes are designed to manipulate one or more of these structure levels. - many scripts fall into more then one catagory. Here is a general listing of some different script types. 'PS Recipes' '- Manipulate and change the sequence of amino acids.' - Mutate sphere - Mutate Combo - Tlaloc mutate - Customised scripts that set the amino acid sequence for different protien puzzles. 'SS Recipes ' '- that manipulate and change the shape of the backbone' - Freestyle hand setting of helices or sheets - Set SS. Sometimes players well make scripts for setting positions of the helix and sheets in a particular protein puzzle. 'Banders.' These recipes make the protein more compact by using bands and forcing parts of the fold in a certain direction by shaking and wiggling with different CI. The parts of the protein they manipulate are chosen randomly. Most used examples are: - Helix curler. Helps to shape the helix. - Compressor. By nature a gentle compressor. - Quaker. A more brute force compressor. - Doom. The real brute force approach. - GA Band. Compressor but the lenght of the bands is calculated differently. - Void Killer. Specific bander which manupilates the area's where voids are. 'Rebuilders.' These recipes rebuild parts of the protein and by manipulating the backbone while constantly checking the score to determine when a rebuild was succesful or not. Mostly used examples are: - DRW. - Loop Rebuild. - walking rebuliders. Settlers. These recipes squeezes out the last (fractions of) points - Walkers. - Repeat settler. - LWS. 'TS Recipes ' '- manipulate and change the positions of sidechains' - Acid Tweekers Side Chain flippers. - These recipes try to find the best side chain position - Side chain flipper - SF 2.2 - snap shake 'QS Recipes' '- that manipulate the isosurface.' So far there are no spacific recipies to change the QS but any script that you run well change the overall shape of the protein's isosurface. Think of how the Docking, Interface, and Symmetric puzzles work. 'Secondary Structures of the Protein.' 'The Alpha Helix' '- '''AAs found most in alpha helix are glutamate, methionine, alanine, and leucine. '''The 'Alpha Helix' structure':*Rigid *Rod-like structure *3.6 amino per turn *Hydrogen bond (N-H- - -O=C) *4 residue ahead (n+4) *Right-handed *1.5 Å translation *100 degrees *Pitch: 54 degree *Average size between 40 to +1000 Å (100nm or 0.1um) A Helix with a twist, right or left? When you look at a helix from the end and the top twist to the left it is a "S" twist helix. A "Z" twist helix well twist to the right at the top when viewed from the end. A "Z" twist helix is happy helix, and a "S" twist helix is a very un-happy helix. Rope and twine making include both "Z" right hand twist strands and a gentler "S" left hand twist to all the bundles of those strands. Both "Z" and "S" twists are essential to stablize the torsional forces produced on a rope when it is stretched. This is the same when forming biological assemblies into larger strands. So the smaller strands are twisted one way, usualy "Z", and the bigger bundles are twisted more gently the other "S" way . Ropes need both "S" and "Z" twists to be stable otherwise if all the strands in a rope or biological structure were all "S" or "Z" twisted, the rope or strand will simply fall apart when pulled on. DNA is triple twisted into very tight compact strands. However unlike biological structures lightbulb filliments are triple twisted helixes, but being made of a flat ribbon of tungstin metal all the helix twist the same way around. 'The Beta Sheet ' '- '''AAs found most in beta sheets are valine, isoleucine, and tyrosine. '''The 'Beta Sheet' structure'*Sheet-like structure *Hydrogen bond (N-H- - -O=C) *Same polypeptide chain *Parallel or non-parallel Roman lock form for sheet order 4u-3d-1d-2u-5d-6u where u=up and d=down This is where the protein strand loops back and forth on itself when making a joining array of sheets. Think of a bears clay pastry like a set of letter CCCCCs all nested together, looping back and forth with the arms being sheets linked by hydrogen bonds all together with long loops going back and forth at the top. Antiparallel & Parallel - sheet forms ' The most comman structural order sheets make are anti-parillel. Meaning that the segment numbers count up down up down. On parrellle sheets, the segment mumbers go up up or down down. On the contact map antiparalle sheets form lines of squares that go from upper left down to lower right. Parallel sheets form a line of squares going the other way from upper right to lower left. 'The B-Turn or U-Turns '- '''AAs found most in reverse b-turns are proline, glycine, aspartate, asparagine, and serine. *Hair-pin or u-turn structure 'Reactive centers -' Sometimes there are reactive centers that are on the outside of a protein. These may be orange sidechains with yellow balls. The yellow balls indicate that these are exposed hydrophobic side chains. Normally you would want these to be turned inward for a better score. Amino Acids (AA) '''AA' (Amino Acid) = The molecular unit in the polypeptide chain. An individual AA is made of a carbonyl and amine group attached to a central tertiary carbon that has either an additional hydrogen atom or arrays of extended sidechain. Some acidic some basic, some polar some non-polar. Some steric. Some aromatic. Each AA has its different configuration. It may varie in its polarity (which attracts water and other polar solvents), its length (stericity), its capabilities for hydrogen bonding, and its aromatic features. Certain AA have a physical structure that makes it best for certain features. For example: Leucine zipper - that form bonds between 2 parille helix. Glycine hinge - forms the bend or u turn in loops at the end of the sheets. Internal AA tend to have sidechains that are non-polar. For example: Myoglobin - the Oxygen-carrying protein in red blood cells has an interior that consists almost entirely of nonpolar residues such as leucine, valine, methionine & phenylaniline. Certain amino acids are found more in certain areas of the protein. For example, Proline is found at the bends of folded proteins. Valine, Leucine & Isoleucine are Hydrophobes. Phenylalamine & Tryptophan are Highly hydrophobe Hydrogen donor: Tryptophan & Arganine Hydrogen donor & acceptor: Asparagine, Glutamine, Serine, Threomine pH-dependent hydrogen D or A: Glutamic acid, Tyrosine, Histidine 'Different t' ypes' of sidechains': *Aliphatic sidechains: Alanine, Valine, Leucine, Glycine, Proline, Isoleucine *Hydroxyl aliphatic: Serine, Threonine *Aromatic sidechains: Phenylalanine, Tryptophan, Tyrosine *Basic sidechains: Lysine, Histidine, Arginine *Acidic sidechains: Glutamic acid, Aspartic acid *Amide sidechains: Asparagine, Glutamine *Sulfur sidechains: Cysteine, Methionine In the polypeptide chain, the rotation between alpha carbon and nitrogen in the backbone is called Phi Φ, and the rotation between alpha carbon and carbonyl carbon is called psi Ψ. Stetic hyndrance, or clashes, prevent certain angles.These can be seen on the Ramachandran plot. ''GENERAL CHEM'' ''ISTRY '' ''- ''how do protein structures form and why. Lets consider aromacity, hydrogen bonds, steric hyndrance, hydrophobicity, disulfide bridge. 'Aromatics' '- ' Aromacity (delocalized pi-bond) Pi-system cluster amongst themselves. Both sulfuric AA (Cysteine & Methionine) are hydrophobic Glycine is the only optically inactive AA Lysine & Arganine are the positively charged and also have the longest sidechain in all the AAs. Amino Acids start with the amino terminal, not the carboxyl terminal. 'How pH can affect AA' AA with amine (hydrogen donor) or carbonyl (hydrogen acceptor) 'Zwitterions:' AAs work as zwitterions.Zwitterions are dipolar molecules. In this case, the dipolarity is found in the carbonyl (negative) and amine (positive) functional group. 'Disulphide bridges' A disulphide bridge is a covalent bond between the two sulfur atoms on each cysteine. The thiol funtional group merges together and a H2 molecule is evolved from the reaction. What was S-H H-S become S-S + H-H. This added bond helps stabilize the structure of a protein. Not all proteins use their cysteines for this purpose, but it should be well taken into consideration. "Intracellular proteins usually lack disulfide bonds, whereas extracellular proteins often contain several." http://en.wikipedia.org/wiki/Cys-loop_receptors 'Chemical bond' type s' 'Covalent bonds ' '- 'A ''covalent bond is a bond in which 2 atoms are sharing pairs of electrons. Strength of covalent bonds differs, but in general they are stronger than hydrogen bonds, van der waals, and static forces. '''The 'two 'types of covalent bonds found in proteins The regular covalent bond linking each peptide in the polypeptide chain of the protein, and all the bonds within the amino acids. The other is found between the 2 cysteines' sulfur atoms: A disulphide bond. Disulphide are an analog of dioxygen (peroxides) which are known for their weak bonds and are used in chemistry for free-radical reactions. ''Hydrogen bonds '' ''- ''Hydrogen bond occurs when 2 atoms are sharing a hydrogen atom.Example in alpha helix and beta sheets: The oxygen atom of a carbonyl group will be the'' hydrogen acceptor'' and the nitrogen of the amine group will be the hydrogen donor. The dipole force is interesting for the "shape" of the hydrogen interaction. Since Oxygen has 2 free electron pairs, it can accept 2 hydrogen for HB. Nitrogen has 1 free pair.Stronger than the regular dipole movement, but weaker than Covalent and Static, being only ~10% as strong as covalent bonds. 'Stericity - ' Van der waals force '- Clashes' Is a force of great repulsion when 2 atoms get closer then 3-4 Å apart. This is caused by an overlap of their electron clouds or isosurface. The further away, the weaker the force. For example: Carbon to Oxygen (C-O) optimal distance = 3.4 Å, which is the the radii of both (1.4 and 2.0 Å)Only about~1Kcal/mol. Low compared to hydrogen bonds. Which compares to the average thermal energy of molecules @ room temperature ~0.6Kcal/molBigger atoms have a larger dispersion force (london force). 'Tempoary fluctuating dipoles' 'Polarity ' or ''' '''Electrostatic bond '- ' Ionic bond, salt linkage, salt bridge, ion pairPolar amino acids tend to attrack water as water is polar. These tend to be on the outside of the protein. 'USEFUL LINKS' . *'Helix' more at http://foldit.wikia.com/wiki/Helix *'Sheet' more at http://foldit.wikia.com/wiki/Sheet *'U-turn' more at http://foldit.wikia.com/wiki/U-Turn *'Disulfide bridge' more at http://foldit.wikia.com/wiki/Disulfide_Bridge *'Glycine hinge' more at http://foldit.wikia.com/wiki/Glycine_Hinge *'hydrophobicity' more at http://foldit.wikia.com/wiki/Hydrophobicity *'hydrogen bonds' more at http://foldit.wikia.com/wiki/Hydrogen_bond http://foldit.wikia.com/wiki/Hydrogen_Bonding*'Disulfide bridge' more at http://foldit.wikia.com/wiki/Disulfide_Bridge *'Steric hyndrance' more at http://en.wikipedia.org/wiki/Steric_effects *'Aromatic interaction' more at http://en.wikipedia.org/wiki/Aromatic_interaction Hinge prediction http://stonehinge.bmb.msu.edu/ http://molmovdb.org/cgi-bin/submit-flexoracle.cgihttp://rigidfinder.molmovdb.org/ Protein motion http://rigidfinder.molmovdb.org/http://molmovdb.org/cgi-bin/movie.cgi